JP2014051480A - Chalcone compound or salt thereof, and bactericidal composition for industrial use - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a novel active ingredient that has excellent controlling effect on microorganism such as bacterium, mold, yeast, algae and the like and to provide a bactericidal composition for industrial use that contains the active ingredient.SOLUTION: A chalcone compound having a substituent at a specific position or a salt thereof has excellent controlling effect on microorganism such as bacterium, mold, yeast, algae and the like.

Description

  The present invention relates to a chalcone compound or a salt thereof, and an industrial bactericidal composition containing the same.

  Conventionally, various industrial waters such as pulp and paper mills, cooling water circulation process; hydrous pulp, coated paper, paper coating liquid, paint, binder, adhesive, latex, ink, etchant, soaking water, wood, fiber, Many industrial products or industrial raw materials such as cement admixtures, sealing agents, resin emulsions, and building materials are prone to the growth of microorganisms such as bacteria and fungi. It is known to be.

  In order to prevent the growth of such microorganisms, various industrial sterilizing compositions having sterilizing, antibacterial, antifungal, antiseptic and antialgal effects have been used. As the compound having the bactericidal action, for example, compounds described in Non-Patent Documents 1 to 3 are known.

  However, the known compounds as described above cannot exhibit the bactericidal effect depending on the type of bacteria or the bactericidal effect is insufficient. Therefore, it has been desired to develop a new active ingredient.

J. Med. Chem., 1998, 41, 1014-1026 Bioorganic & Medicinal Chemistry, 12 (2004), 3047-3054 Pharmazie, 46 (1991), H.10

  The subject of this invention is providing the novel active ingredient which has the outstanding control effect with respect to microorganisms, such as bacteria, mold | fungi, yeast, algae, and the industrial sterilization composition containing it.

  In view of the above problems, the present inventors have conducted extensive research to develop a novel active ingredient, and as a result, the novel chalcone compound or a salt thereof is superior to microorganisms such as bacteria, molds, yeasts, and algae. It was found to have a control effect.

That is, this invention relates to the chalcone-type compound shown below or its salt, and the industrial disinfection composition containing it.
Item 1. A chalcone compound represented by the following general formula (1) or a salt thereof.

(In the formula, R ¹ represents a hydrogen atom, a halogen atom or a carboxyl group; R ² represents a hydrogen atom, a halogen atom, a carboxyl group, a hydroxyl group, an alkoxy group, a C _1-4 alkyl group or a nitro group; R ³ represents a hydrogen atom, a halogen atom, a carboxyl group, a hydroxyl group, an alkoxy group, a C _1-4 alkyl group or a nitrogen-containing heterocyclic ring, and A represents —CH═CH— or —CHX ¹ —CHX ² —. X ¹ and X ² are the same or different and each represents a hydrogen atom or a halogen atom, provided that when A represents —CH═CH— and R ³ represents a carboxyl group or a hydroxyl group, R ¹ represents hydrogen. Not an atom.)
Item 2. In the general formula (1), the chalcone compound is
(I) a compound wherein A represents —CH═CH—, R ¹ and R ² are as defined above, and R ³ represents a C _1-4 alkyl group,
(Ii) A compound in which A represents —CHX ¹ —CHX ² —, R ¹ or R ² represents a halogen atom, and R ³ is as defined above,
(Iii) A represents —CHX ¹ —CHX ² —, R ¹ is as defined above, R ² or R ³ represents a carboxyl group, and (iv) A represents —CHX ¹ —CHX ² —. A compound in which R ¹ is the same as defined above, and R ² or R ³ represents a hydroxyl group,
Item 2. The chalcone compound or a salt thereof according to item 1, which is one selected from the group consisting of:
Item 3. A method for producing a chalcone compound represented by the following general formula (1a) or a salt thereof,

（式中、R¹は、水素原子、ハロゲン原子又はカルボキシル基を示し、R²は、水素原子、ハロゲン原子、カルボキシル基、水酸基、アルコキシ基、C_1-4のアルキル基又はニトロ基を示し、R³は、水素原子、ハロゲン原子、カルボキシル基、水酸基、アルコキシ基、C_1-4のアルキル基又は含窒素複素環を示す。但し、R³が、カルボキシル基又は水酸基を示す場合、R¹は、水素原子ではない。）
下記一般式（２）で表されるアセトフェノン化合物と、

(In the formula, R ¹ represents a hydrogen atom, a halogen atom or a carboxyl group; R ² represents a hydrogen atom, a halogen atom, a carboxyl group, a hydroxyl group, an alkoxy group, a C _1-4 alkyl group or a nitro group; R ³ represents a hydrogen atom, a halogen atom, a carboxyl group, a hydroxyl group, an alkoxy group, a C _1-4 alkyl group or a nitrogen-containing heterocyclic ring, provided that when R ³ represents a carboxyl group or a hydroxyl group, R ¹ is , Not a hydrogen atom.)
An acetophenone compound represented by the following general formula (2);

（式中、R¹は、水素原子、ハロゲン原子又はカルボキシル基を示し、R²は、水素原子、ハロゲン原子、カルボキシル基、水酸基、アルコキシ基、C_1-4のアルキル基又はニトロ基を示し、R³は、水素原子、ハロゲン原子、カルボキシル基、水酸基、アルコキシ基、C_1-4のアルキル基又は含窒素複素環を示す。但し、R³が、カルボキシル基又は水酸基を示す場合、R¹は、水素原子ではない。）
下記一般式（３）で表されるベンゾフェノン化合物とを、塩基存在下に溶媒中で反応させる、

(In the formula, R ¹ represents a hydrogen atom, a halogen atom or a carboxyl group; R ² represents a hydrogen atom, a halogen atom, a carboxyl group, a hydroxyl group, an alkoxy group, a C _1-4 alkyl group or a nitro group; R ³ represents a hydrogen atom, a halogen atom, a carboxyl group, a hydroxyl group, an alkoxy group, a C _1-4 alkyl group or a nitrogen-containing heterocyclic ring, provided that when R ³ represents a carboxyl group or a hydroxyl group, R ¹ is , Not a hydrogen atom.)
A benzophenone compound represented by the following general formula (3) is reacted in a solvent in the presence of a base;

カルコン系化合物又はその塩の製造方法。
項４．下記一般式（１ｂ）で表されるカルコン系化合物又はその塩を製造する方法であって、

A method for producing a chalcone compound or a salt thereof.
Item 4. A method for producing a chalcone compound represented by the following general formula (1b) or a salt thereof,

（式中、R¹は、水素原子、ハロゲン原子又はカルボキシル基を示し、R²は、水素原子、ハロゲン原子、カルボキシル基、水酸基、アルコキシ基、C_1-4のアルキル基又はニトロ基を示し、R³は、水素原子、ハロゲン原子、カルボキシル基、水酸基、アルコキシ基、C_1-4のアルキル基又は含窒素複素環を示す。X¹及びX²は同一又は異なって、水素原子又はハロゲン原子を示す。）
下記一般式（１ａ）で表されるカルコン系化合物に付加処理を行う、

(In the formula, R ¹ represents a hydrogen atom, a halogen atom or a carboxyl group; R ² represents a hydrogen atom, a halogen atom, a carboxyl group, a hydroxyl group, an alkoxy group, a C _1-4 alkyl group or a nitro group; R ³ represents a hydrogen atom, a halogen atom, a carboxyl group, a hydroxyl group, an alkoxy group, a C _1-4 alkyl group or a nitrogen-containing heterocyclic ring, and X ¹ and X ² are the same or different and each represents a hydrogen atom or a halogen atom. Show.)
An addition treatment is performed on the chalcone compound represented by the following general formula (1a).

（式中、R¹は、水素原子、ハロゲン原子又はカルボキシル基を示し、R²は、水素原子、ハロゲン原子、カルボキシル基、水酸基、アルコキシ基、C_1-4のアルキル基又はニトロ基を示し、R³は、水素原子、ハロゲン原子、カルボキシル基、水酸基、アルコキシ基、C_1-4のアルキル基又は含窒素複素環を示す。但し、R³が、カルボキシル基又は水酸基を示す場合、R¹は、水素原子ではない。）
カルコン系化合物又はその塩の製造方法。
項５．項１又は２に記載のカルコン系化合物又はその塩を含有する工業用殺菌組成物。

(In the formula, R ¹ represents a hydrogen atom, a halogen atom or a carboxyl group; R ² represents a hydrogen atom, a halogen atom, a carboxyl group, a hydroxyl group, an alkoxy group, a C _1-4 alkyl group or a nitro group; R ³ represents a hydrogen atom, a halogen atom, a carboxyl group, a hydroxyl group, an alkoxy group, a C _1-4 alkyl group or a nitrogen-containing heterocyclic ring, provided that when R ³ represents a carboxyl group or a hydroxyl group, R ¹ is , Not a hydrogen atom.)
A method for producing a chalcone compound or a salt thereof.
Item 5. Item 3. An industrial sterilizing composition comprising the chalcone compound or a salt thereof according to Item 1 or 2.

  Since the chalcone compound or salt thereof of the present invention has an excellent control effect against microorganisms such as bacteria, molds, yeasts, and algae, it can be used as an active ingredient in industrial sterilizing compositions.

  The industrial sterilizing composition containing the chalcone compound of the present invention or a salt thereof is excellent in sterilizing, antibacterial, antifungal, antiseptic and antialgal effects, and therefore is used as a control agent for microorganisms such as bacteria, molds, yeasts and algae. Useful.

Hereinafter, the present invention will be described in detail.
1. Chalcone compound or salt thereof The chalcone compound or salt thereof of the present invention is a compound represented by the following general formula (1).

（式中、R¹は、水素原子、ハロゲン原子又はカルボキシル基を示し、R²は、水素原子、ハロゲン原子、カルボキシル基、水酸基、C_1-4のアルコキシ基、C_1-4のアルキル基又はニトロ基を示し、R³は、水素原子、ハロゲン原子、カルボキシル基、水酸基、C_1-4のアルコキシ基、C_1-4のアルキル基又は含窒素複素環を示す。Aは、−CH＝CH−又は−CHX¹−CHX²−を示し、X¹及びX²は同一又は異なって、水素原子又はハロゲン原子を示す。但し、Aが−CH＝CH−を示し、R³が、カルボキシル基又は水酸基を示す場合、R¹は、水素原子ではない。）

(In the formula, R ¹ represents a hydrogen atom, a halogen atom or a carboxyl group, and R ² represents a hydrogen atom, a halogen atom, a carboxyl group, a hydroxyl group, a C _1-4 alkoxy group, a C _1-4 alkyl group, or Represents a nitro group, R ³ represents a hydrogen atom, a halogen atom, a carboxyl group, a hydroxyl group, a C _1-4 alkoxy group, a C _1-4 alkyl group, or a nitrogen-containing heterocyclic ring, and A represents —CH═CH - or -CHX ¹ -CHX ² -. indicates, X ¹ and X ² are the same or different and represent a hydrogen atom or a halogen atom provided that, a represents -CH = CH-, R ³ is a carboxyl group or a When it represents a hydroxyl group, R ¹ is not a hydrogen atom.)

  Examples of the halogen atom include fluorine, chlorine, bromine, bromine and the like. Preferred is bromine.

Examples of the C _1-4 alkyl group include a linear or branched alkyl group having 1 to 4 carbon atoms. Specific examples include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, and a t-butyl group. An isopropyl group is preferred.

Examples of the C _1-4 alkoxy group include linear or branched alkoxy groups having 1 to 4 carbon atoms. Specific examples include a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, and a t-butoxy group.

  As a nitrogen-containing heterocyclic ring, the 5-membered heterocyclic compound containing 1-4 nitrogen as a hetero atom is mentioned, for example. Specific examples include pyrrole, imidazole, pyrazole, imidazoline, pyrazine, triazole, tetrazole and the like. Tetrazole is preferred.

In the chalcone compound represented by the general formula (1), when A is —CH═CH—, R ¹ represents a hydrogen atom, R ² represents a hydrogen atom, a carboxyl group, a hydroxyl group, or a nitro group, R ³ is preferably a compound showing a hydrogen atom, a C _1-4 alkyl group, a carboxyl group, a hydroxyl group or a nitrogen-containing heterocyclic ring. R ¹ represents a hydrogen atom, a halogen atom or a carboxyl group, and R ² represents a hydrogen atom, a halogen atom, a carboxyl group, a hydroxyl group, a C _1-4 alkoxy group, a C _1-4 alkyl group or a nitro group. Also preferred are compounds wherein R ³ represents a C _1-4 alkyl group.

Particularly preferably, a compound in which R ¹ and R ³ are hydrogen atoms and R ² is a carboxyl group; a compound in which R ¹ and R ² are hydrogen atoms and R ³ is a C _1-4 alkyl group A compound in which R ¹ and R ³ are hydrogen atoms and R ² is a hydroxyl group; a compound in which R ¹ and R ² are hydrogen atoms and R ³ is a nitrogen-containing heterocycle; R ¹ is a hydrogen atom; A compound in which R ² is a carboxyl group and R ³ is a hydroxyl group; R ¹ is a hydrogen atom, R ² is a nitro group, and R ³ is a hydroxyl group.

In the chalcone compound represented by the general formula (1), when A is —CHX ¹ —CHX ² —, R ¹ represents a hydrogen atom, a halogen atom or a carboxyl group, and R ² represents a hydrogen atom or a halogen atom. And a compound in which R ³ represents a hydrogen atom, a halogen atom, a carboxyl group, a hydroxyl group, or a C _1-4 alkyl group. A compound in which R ¹ or R ² represents a halogen atom, and R ³ is a hydrogen atom, a halogen atom, a carboxyl group, a hydroxyl group, a C _1-4 alkoxy group, a C _1-4 alkyl group, or a nitrogen-containing heterocyclic ring. R ¹ represents a hydrogen atom, a halogen atom or a carboxyl group, R ² or R ³ represents a carboxyl group, R ¹ represents a hydrogen atom, a halogen atom or a carboxyl group, and R ² or R ³ represents a hydroxyl group Also preferred are compounds.

Particularly preferably, a compound in which any one of R ¹ , R ² and R ³ is a halogen atom, the remaining two are hydrogen atoms, and X ¹ and X ² are halogen atoms; R ¹ , R ² and R ³ A compound in which any one of them is a carboxyl group and the remaining two are hydrogen atoms, and X ¹ and X ² are halogen atoms; R ¹ is a hydrogen atom, and any one of R ² and R ³ is a hydroxyl group Wherein the remaining one is a hydrogen atom and X ¹ and X ² are halogen atoms; a compound in which R ¹ , R ² , X ¹ and X ² are hydrogen atoms and R ³ is a hydroxyl group; R ¹ , R ² is a hydrogen atom, R ³ is a C _1-4 alkyl group, X ¹ and X ² are halogen atoms; R ¹ is a hydrogen atom, R ² is a nitro group, R ³ is a hydroxyl group, X ¹ And a compound wherein X ² is a halogen atom; a compound wherein R ¹ is a hydrogen atom, R ² is a C _1-4 alkyl group, R ³ is a hydroxyl group, and X ¹ and X ² are halogen atoms; R ¹ is a hydrogen atom; R ² , X ¹ and X ² are halogen atoms, and R ³ is a hydroxyl group.

Among the chalcone compounds represented by the above general formula (1), a compound or a salt thereof, in which A represents —CHX ¹ —CHX ² — and R ² or R ³ represents a hydroxyl group, is preferable.

  Of the chalcone compounds represented by the general formula (1), a compound having an acidic group can form a salt with a basic compound. Examples of such basic compounds include metal hydroxides, alkali metal carbonates or bicarbonates, alkali metal alcoholates, and the like.

  Specific examples of the metal hydroxide include lithium hydroxide, sodium hydroxide, potassium hydroxide, and calcium hydroxide.

  Specific examples of the alkali metal carbonate or bicarbonate include sodium carbonate and sodium bicarbonate.

  Specific examples of the alkali metal alcoholate include sodium methylate and potassium ethylate.

  Of the chalcone compounds represented by the general formula (1), a compound having a basic group can form a salt with an acid. Examples of such acids include inorganic acids and organic acids.

  Specific examples of the inorganic acid include sulfuric acid, nitric acid, hydrochloric acid, hydrobromic acid and the like.

  Specific examples of the organic acid include acetic acid, p-toluenesulfonic acid, ethanesulfonic acid, oxalic acid, maleic acid, fumaric acid, citric acid, succinic acid, benzoic acid and the like.

  In the present invention, the salt can also be used as an active ingredient in the same manner as the chalcone compound represented by the general formula (1) in free form.

2. Production method of chalcone compound or salt thereof Of the chalcone compound or salt thereof represented by the above general formula (1) of the present invention, A is represented by the following general formula (1a) wherein -CH = CH-. The compound represented by the following general formula (2) is known or can be easily produced from a known raw material (for example, see Example 4 below), an acetophenone compound, and the following general formula (3) It can manufacture by making the well-known benzaldehyde compound represented by these react in a solvent in presence of a base.

（式中、R¹、R²及びR³は、上記一般式（１）におけるR¹、R²及びR³と同じであり、R³が、カルボキシル基又は水酸基を示す場合、R¹は、水素原子ではない。）

(Wherein, R ^1, R ² and R ³ are the same as R ^1, R ² and R ³ in the general formula (1), if indicated R ³ is a carboxyl group or a hydroxyl group, R ¹ is Not a hydrogen atom.)

（式中、R¹、R²及びR³は、上記一般式（１）におけるR¹、R²及びR³と同じであり、R³が、カルボキシル基又は水酸基を示す場合、R¹は、水素原子ではない。）

(Wherein, R ^1, R ² and R ³ are the same as R ^1, R ² and R ³ in the general formula (1), if indicated R ³ is a carboxyl group or a hydroxyl group, R ¹ is Not a hydrogen atom.)

  As the solvent used in the reaction of the compound represented by the general formula (2) and the compound represented by the general formula (3), a known solvent is widely used as long as it is an inert solvent for the reaction. can do. For example, ether solvents such as diethyl ether, diisopropyl ether, tetrahydrofuran, 1,4-dioxane, dimethoxyethane, diethylene glycol dimethyl ether, methyl-tert-butyl ether, methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, Examples thereof include alcohol solvents such as sec-butanol, tert-butanol, ethanediol, methoxyethanol, ethoxyethanol, diethylene glycol monomethyl ether, and diethylene glycol monoethyl ether, and water. These solvents are used alone or in combination of two or more. Among these, a combination of an alcohol solvent and water is preferable, and a mixed solvent of ethanol and water is particularly preferable.

  These solvents are generally used in an amount of about 1 to 100 parts by weight, preferably about 10 to 20 parts by weight per 1 part by weight of the compound represented by the general formula (2).

  The reaction of the compound represented by the general formula (2) and the compound represented by the general formula (3) is performed in the presence of a base. Examples of the base include sodium hydroxide, potassium hydroxide, sodium methoxide, sodium ethoxide and the like. Sodium hydroxide is preferable.

  The base is usually used in an amount of about 7 to 30 parts by weight, preferably about 8 to 15 parts by weight, based on 1 part by weight of the compound represented by the general formula (2). It is preferable to use it with a solvent as a 10% aqueous sodium hydroxide solution.

  The ratio of the compound represented by the general formula (2) and the compound represented by the general formula (3) can be appropriately selected from a wide range, but the latter is 1 per 1 mol of the former. It is preferable to use 0.0 mol or more, and it is more preferable to use 1.5 to 3.0 mol.

  This reaction can be normally performed at 0-80 degreeC. The reaction is preferably performed at 0 to 30 ° C, and more preferably at room temperature.

  The reaction time varies depending on the type of raw material compound and the reaction temperature, and cannot be generally specified, but is usually about 12 to 24 hours.

Of the chalcone compounds represented by the above general formula (1) or salts thereof according to the present invention, the compound represented by the following general formula (1b) wherein A is —CHX ¹ —CHX ² — It can be produced by addition reaction of the compound represented by 1a).

（式中、R¹、R²、R³、X¹及びX²は、上記一般式（１）におけるR¹、R² 、R³、X¹及びX²と同じである。）

(Wherein, ^{R 1, R 2, R 3} , X 1 and X ² are the same as ^{R 1, R 2, R 3} , X 1 and X ² in the general formula (1).)

  Examples of the addition reaction of the compound represented by the general formula (1a) include a catalytic hydrogenation reaction and a halogenation reaction.

  The catalytic hydrogenation reaction is a method represented by the following reaction formula-1.

（式中、R¹、R²及びR³は、上記一般式（１）におけるR¹、R²及びR³と同じである。）

(Wherein, R ^1, R ² and R ³ are the same as R ^1, R ² and R ³ in the general formula (1).)

  In the method shown in Reaction Scheme-1, hydrogen molecules are added to the alkene moiety by a catalytic hydrogenation reaction. For example, hydrogen is added using a metal such as nickel, platinum, palladium, rhodium, and ruthenium as a catalyst. Known catalytic hydrogenation reaction conditions can be widely applied to the catalytic hydrogenation reaction.

  The halogenation reaction is a method represented by the following reaction formula-2.

（式中、R¹、R²及びR³は、上記一般式（１）におけるR¹、R²及びR³と同じである。Xは、X¹又はX²と同じである。）

(Wherein, R ^1, R ² and R ³ are the same as R ^1, R ² and R ³ in the general formula (1) .X is the same as X ¹ or X ^2.)

  In the method shown in Reaction Scheme-2, a halogen is added to the alkene moiety by a halogenation reaction. For example, halogen is added using chloroform as a solvent. Known halogenation reaction conditions can be widely applied to the halogenation reaction.

In the reaction, when R ² and / or R ^{3 of the} compound represented by the general formula (1a) as a raw material is a hydroxyl group, a halogenation reaction is performed after protecting the hydroxyl group in advance, if necessary. You can also.

  As the hydroxyl-protecting group, conventionally known ones can be used. For example, t-butoxycarbonyl group (Boc group), methyl group, methoxymethyl group (MOM group), t-butyl group, t-butyldimethyl A silyl group (TBS group), a triisopropylsilyl group (TIPS group), a t-butyldiphenylsilyl group (TBDPS group), etc. are mentioned. The protective group for the hydroxyl group can be removed from the hydroxyl group by a conventionally known deprotection reaction after the halogenation reaction.

  The compounds obtained by the above various reactions can be separated from the reaction system by ordinary separation means and further purified. Examples of the separation and purification means include distillation method, recrystallization method, solvent extraction method, column chromatography, ion exchange chromatography, gel chromatography, affinity chromatography, preparative chromatography and the like.

3. Industrial sterilization composition The industrial sterilization composition of the present invention contains, as an active ingredient, at least one selected from the group consisting of chalcone compounds represented by the above general formula (1) or salts thereof.

  The content of at least one selected from the group consisting of chalcone compounds represented by the general formula (1) or a salt thereof in the industrial sterilization composition of the present invention is not particularly limited, but is usually 0.00005. About 100% by weight, preferably about 0.01-60% by weight, more preferably about 0.1-30% by weight. The industrial sterilizing composition of the present invention may be composed of a chalcone compound represented by the general formula (1) or a salt thereof (that is, 100%).

  The active ingredient can be used as a powder as it is, or the active ingredient can be dissolved in a solvent and provided as a liquid. A dissolution aid may be used for dissolution. Moreover, it can also be provided as a suspending agent or a dispersing agent by suspending or dispersing using a surfactant or the like. Furthermore, it can be emulsified with a surfactant and provided as an emulsion. In addition, a surfactant or a solid carrier can be added to provide a wettable powder, flowable powder, powder, or pellet.

  Examples of the solvent include water, lower alcohols, polyhydric alcohols, ketones, ethers, esters, aromatic solvents, halogenated hydrocarbon solvents, polar organic solvents, and the like.

  Specific examples of the lower alcohol include methanol, ethanol, n-propanol, isopropanol, and n-butanol.

  Specific examples of the polyhydric alcohol include ethylene glycol, diethylene glycol, polyethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, 1,3-butanediol, 1,4-butanediol, 1,5-pentanediol, Examples include ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, diethylene glycol monomethyl ether, and diethylene glycol monoethyl ether.

  Specific examples of the ketone include acetone, methyl ethyl ketone, methyl isobutyl ketone, and propylene carbonate.

  Specific examples of the ether include dioxane, tetrahydrofuran, diethyl ether and the like.

  Specific examples of the ester include ethyl acetate, butyl acetate, isobutyl acetate, 3-methyl-3-methoxybutyl acetate, γ-butyrolactone, dimethyl adipate, dimethyl glutarate, and dimethyl succinate.

  Specific examples of the aromatic solvent include benzene, toluene, xylene, methylnaphthalene, dimethylnaphthalene, isopropylnaphthalene, diisopropylnaphthalene, ethylbiphenyl, diethylbiphenyl, and solvent naphtha.

  Specific examples of the halogenated hydrocarbon solvent include carbon tetrachloride, chloroform, and methylene chloride.

  Specific examples of the polar organic solvent include dimethylformamide, dimethylacetamide, dimethylsulfoxide, acetonitrile, N-methylpyrrolidone and the like.

  Among these, water, lower alcohol, and polyhydric alcohol are preferable.

  These solvents can be used alone or in combination of two or more as required.

  About 40 to 99% by weight of the solvent is used with respect to the total amount of the industrial sterilizing composition.

  Examples of the dissolution aid include carboxylic acid, higher fatty acid ester, higher alcohol, and amine.

  Specific examples of the carboxylic acid include capric acid and adipic acid.

  Specific examples of the higher fatty acid ester include diisopropyl adipate, diisopropyl sebacate, isopropyl myristate, and isopropyl palmitate.

  Specific examples of the higher alcohol include octyldodecanol and oleyl alcohol.

  Specific examples of the amine include monoethanolamine and diethanolamine.

  These dissolution aids can be used alone or in combination of two or more as required.

  When using a solubilizing agent, the compounding quantity with respect to the industrial sterilization composition whole quantity is about 0.1 to 10 weight%.

  Examples of the surfactant include nonionic surfactants and anionic surfactants.

  Specific examples of the nonionic surfactant include polyoxyethylene alkyl ether, polyoxyethylene sorbitan alkyl ester, polyoxyethylene nonylphenyl ether, polyoxyethylene polyoxypropylene glycol and the like.

  Specific examples of anionic surfactants include alkyl sulfate esters, alkyl (aryl) sulfonates, dialkyl sulfosuccinates, polyoxyethylene alkylaryl ether phosphate esters, lignin sulfonates, and naphthalene sulfones. Examples include acid formalin condensates.

  These surfactants can be used individually by 1 type, or can be used in mixture of 2 or more type as needed.

  When using surfactant, the compounding quantity with respect to the industrial sterilization composition whole quantity is about 0.1 to 10 weight%.

  Examples of the solid carrier include fine powders or granular materials such as mineral substances, natural organic substances, synthetic organic substances, inorganic salts, and synthetic inorganic substances.

  Specific examples of minerals include kaolin clay, attapulgite clay, bentonite, montmorillonite, acid clay, pyrophyllite, talc, diatomaceous earth, and calcite.

  Specific examples of the natural organic material include corn cob flour and walnut shell flour.

  Specific examples of the synthetic organic substance include urea.

  Specific examples of the inorganic salt include calcium carbonate and ammonium sulfate.

  Specific examples of the synthetic inorganic substance include synthetic silicon hydroxide.

  When using a solid support, the compounding quantity with respect to the industrial sterilization composition whole quantity is about 30 to 90 weight%.

  Preparation of the industrial sterilizing composition of the present invention may be performed under cooling, at room temperature, or under heating, and preferably at 5 to 40 ° C.

  Furthermore, the industrial bactericidal composition of the present invention includes known additives such as anti-algae and / or an antibacterial agent within the range that does not affect the antibacterial activity and stability of the composition, depending on the purpose and application. In addition to an antifungal agent (active ingredient), additives generally used for formulation, such as a pH adjuster, an antioxidant, a light stabilizer, and an antifoaming agent, can be added.

  Examples of the algae and / or fungicide include, for example, isothiazoline compounds, nitroalcohol compounds, dithiol compounds, thiophene compounds, haloacetylene compounds, phthalimide compounds, haloalkylthio compounds, pyrithione compounds, phenyl Examples include urea compounds, triazine compounds, guanidine compounds, triazole compounds, benzimidazole compounds, quaternary ammonium salt compounds, and the like.

  Specific examples of the isothiazoline-based compound include 2-methyl-4-isothiazolin-3-one, 2-n-octyl-4-isothiazolin-3-one, and 5-chloro-2-methyl-4-isothiazoline-3. -One, 5-chloro-2-n-octyl-4-isothiazolin-3-one, 4-chloro-2-n-octyl-4-isothiazolin-3-one, 4,5-dichloro-2-n-octyl -4-isothiazolin-3-one, 2-methyl-4,5-trimethylene-4-isothiazolin-3-one, 1,2-benzisothiazolin-3-one, Nn-butyl-1,2-benzisothiazoline -3-one etc. are mentioned.

  Specific examples of the nitroalcohol compound include 2-bromo-2-nitropropane-1,3-diol, 2,2-dibromo-2-nitro-1-ethanol, and the like.

  Specific examples of the dithiol-based compound include 4,5-dichloro-1,2-dithiol-3-one.

  Specific examples of the thiophene compound include 3,3,4-trichlorotetrahydrothiophene-1,1-dioxide, 3,3,4,4-tetrachlorotetrahydrothiophene-1,1-dioxide and the like.

  Specific examples of the haloacetylene compound include N-butyl-3-iodopropiolic acid amide, 3-iodo-2-propynylbutylcarbamate, and the like.

  Specific examples of the phthalimide-based compound include N-1,1,2,2-tetrachloroethylthio-tetrahydrophthalimide (Captafol), N-trichloromethylthio-tetrahydrophthalimide (Captan), and N-dichlorofluoromethylthiophthalimide (Fluorolpet). N-trichloromethylthiophthalimide (Folpet) and the like.

  Specific examples of the haloalkylthio compounds include N-dimethylaminosulfonyl-N-tolyl-dichlorofluoromethanesulfamide (Tolylfluoride), N-dimethylaminosulfonyl-N-phenyl-dichlorofluoromethanesulfamide (Dichlofluoride). ) And the like.

  Specific examples of the pyrithione compound include sodium pyrithione and zinc pyrithione.

  Specific examples of the phenylurea compound include 3- (3,4-dichlorophenyl) -1,1-dimethylurea.

  Specific examples of the triazine compound include 2-methylthio-4-t-butylamino-6-cyclopropylamino-s-triazine.

  Specific examples of the guanidine-based compound include 1,6-di- (4'-chlorophenyldiguanide) -hexane, polyhexamethylene biguanidine hydrochloride and the like.

  Specific examples of the triazole compound include α- [2- (4-chlorophenyl) ethyl] -α- (1,1-dimethylethyl) -1H-1,2,4-triazole-1-ethanol (conventional use). Name: tebuconazole), 1-[[2- (2,4-dichlorophenyl) -4-n-propyl-1,3-dioxolan-2-yl] methyl] -1H-1,2,4-triazole (common name) : Propiconazole), 1-[[2- (2,4-dichlorophenyl) -1,3-dioxolan-2-yl] methyl] -1H-1,2,4-triazole (common name: azaconazole), α -(4-Chlorophenyl) -α- (1-cyclopropylethyl) -1H-1,2,4-triazole-1-ethanol (common name: cyproconazole) and the like.

  Specific examples of the benzimidazole compound include methyl-2-benzimidazole carbamate, ethyl-2-benzimidazole carbamate, and 2- (4-thiazolyl) benzimidazole.

  Specific examples of the quaternary ammonium salt compound include hexadecyltrimethylammonium bromide, hexadecyltrimethylammonium chloride, benzalkonium chloride, di-n-decyl-dimethylammonium chloride, 1-hexadecylpyridinium chloride and the like. It is done.

  Further, as other algae and / or antifungal agents, for example, organic iodine compounds such as diiodomethyl-p-toluylsulfone, p-chlorophenyl-3-iodopropargyl formal, and thiocarbamate compounds such as tetramethylthiuram disulfide Compounds, nitrile compounds such as 2,4,5,6-tetrachloroisophthalonitrile, pyridine compounds such as 2,3,5,6-tetrachloro-4- (methylsulfonyl) pyridine, 2- (4- Benzothiazole compounds such as thiocyanomethylthio) benzothiazole, oxathiazine compounds such as 3-benzo [b] thien-2-yl-5,6-dihydro-1,4,2-oxathiazine-4-oxide, Cyanoacetamide compounds such as 2-dibromo-3-nitrilopropanamide, methylene Thiocyanate compounds such as Suchioshianeto like.

  These algae and / or antifungal agents can be used singly or in combination of two or more as required. Preferably, an isothiazoline-based compound (2-n-octyl-4-isothiazolin-3-one, 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one, Nn-butyl-1,2 -Benzisothiazoline-3-one), haloacetylene compound (3-iodo-2-propynylbutylcarbamate), pyrithione compound (zinc pyrithione), phenylurea compound (3- (3,4-dichlorophenyl) -1,1 -Dimethylurea), triazine compound (2-methylthio-4-t-butylamino-6-cyclopropylamino-s-triazine), triazole compound (α- [2- (4-chlorophenyl) ethyl] -α- (1,1-dimethylethyl) -1H-1,2,4-triazole-1-ethanol (common name: tebuconazo ))) And a benzimidazole compound (methyl-2-benzimidazole carbamate), a synergistic microorganism control effect can be exhibited.

  In addition, the blending ratio of the algae and / or antifungal agent is appropriately selected depending on the dosage form, purpose and application, for example, 1 to 9000 parts by weight, preferably 100 parts by weight of chalcone compound, 3 to 8000 parts by weight.

  Examples of the antioxidant include phenol-based antioxidants such as 2,6-di-t-butyl-4-methylphenol and 2,2′-methylenebis (4-methyl-6-t-butylphenol), alkyldiphenylamine And amine-based antioxidants such as N, N′-di-s-butyl-p-phenylenediamine.

  These antioxidants can be used individually by 1 type, or can be used in mixture of 2 or more type as needed.

  Further, the blending ratio of the antioxidant is not particularly limited and is appropriately selected depending on the dosage form, purpose and application. For example, when formulated as a liquid, it is 0.00% relative to 100 parts by weight of the liquid. 1-5 parts by weight are added.

  Examples of the light stabilizer include hindered amine light stabilizers such as bis (2,2,6,6-tetramethyl-4-piperidyl) sebacate.

  A light stabilizer can be used individually by 1 type, or can mix and use 2 or more types as needed.

  Further, the blending ratio of the light stabilizer is not particularly limited, and is appropriately selected depending on the dosage form, purpose and application. For example, when formulated as a liquid, it is 0.1% relative to 100 parts by weight of the liquid. 1-10 parts by weight are added.

2. Application object The industrial sterilizing composition of the present invention is blended in an industrial product or used as a slime control agent in industrial water.

Industrial Products The industrial products refer to conventionally known industrial products and industrial raw materials. Examples of industrial products include paints, adhesives, inks, sealing agents, coated papers, and the like. Examples of industrial raw materials include latex, paper coating liquid, binder, etchant, resin emulsion, pigment, dye, fiber oil, water-containing pulp, fiber oil, and the like.

  Moreover, the industrial disinfecting composition of the present invention can also be applied to industrial water. More specifically, it can also be used as a slime control agent in industrial water such as water, circulating water and cooling water in the papermaking process.

Related industrial disinfectant composition of species present invention, with respect to known microorganisms show a wide range antimicrobial effect.

  Examples of the microorganism include bacteria and fungi.

  Examples of the bacteria include gram-negative bacilli, gram-positive bacilli, gram-negative cocci, and gram-positive cocci.

  Specific examples of the Gram-negative bacilli include bacteria such as Escherichia genus, Pseudomonas genus, Burkholderia genus (Burkholderia genus), Serratia genus (Serratia genus), and the like.

  Specific examples of Gram-positive rods include bacteria such as Bacillus genus and Clostridium genus.

  Specific examples of gram-negative cocci include bacteria such as the genus Branhamella.

  Specific examples of the gram-positive cocci include bacteria such as Staphylococcus (genus Staphylococcus).

  Examples of the fungi include molds and yeasts.

  Specifically, molds such as Penicillium (genus Penicillium), Cladosporium (Cladosporium), Aureobasidium (Aureobasidium), Alternaria (Alternaria), Gliocladium (Gliocladium), etc. Is mentioned.

  Specific examples of yeast include yeasts of the genus Rhodotorula (genus Rhodotorula) and the genus Saccharomyces (genus Saccharomyces).

Application amount The application amount of the industrial sterilization composition of the present invention may be appropriately selected according to the application object (type of industrial product, type of microorganism, etc.) and the control period.

  For example, when blended with an industrial product, the amount of the active ingredient may be 10 to 50000 mg, preferably 100 to 10,000 mg per kg of the industrial product.

  Moreover, when using as a slime control agent, what is necessary is just to mix | blend so that it may become 1-50000 mg as an amount of an active ingredient with respect to 1 kg of industrial water, Preferably, it will be 5-1000 mg.

  Hereinafter, the present invention will be described in more detail with reference to examples. However, the present invention is not limited to the following examples.

Example 1
3.65 g (10.0 mmol) of 3′-carboxyacetophenone and 1.0 ml (10.2 mmol) of benzaldehyde were dissolved in 10 ml of 10 wt% aqueous sodium hydroxide solution and 10 ml of ethanol, and stirred at room temperature for 24 hours. To this reaction solution, 200 ml of water and 20 ml of 1M hydrochloric acid were added and extracted with 50 ml of chloroform. After desolvation, 3′-carboxychalcone (C ₁₆ H ₁₂ O ₃ ) was obtained as a pale yellow solid.
Yield: 2.0 g, Yield: 80%, Melting point: 153.5-155.7 ° C
IR (KBr): 3025 (ν _ArC-H ), 2569 (ν _OH ), 1680 (ν _{C = O} ), 1657 (ν _{C = O} ), 1610 (ν _{C = C} ), 1418 (δ _OH ), 1216 (ν _CO ), 746 and 681 cm ^-1 (γ _CH ).
¹ H-NMR (δ, CDCl ₃ , 500 MHz): 7.43-7.45 (3H, m, C _3,4,5- H), 7.56-7.69 (4H, m, C _{α, 2, 6,5 '} -H ), 7.87 (1H, d, J = 16 Hz, C _β -H), 8.25-8.32 (2H, m, C _{4 ', 6'} -H), and 8.72 ppm (1H, s, C _{2 '} -H ).
Elemental analysis (EA): C ₁₆ H ₁₂ O ₃・ 0.5H ₂ O
Theoretical value: C, 73.55%, H, 5.02%
Actual value: C, 73.29%, H, 5.06%

Example 2
4′-Isopropylacetophenone 1.7 ml (10.1 mmol) and benzaldehyde 1.0 ml (10.2 mmol) were dissolved in 10 wt% aqueous sodium hydroxide solution 10 ml and ethanol 10 ml and stirred at room temperature for 24 hours. To this reaction solution, 100 ml of water was added and extracted with 80 ml of chloroform. After removing the solvent, the obtained crude product was purified by silica gel column chromatography (silica gel: 70 g, developing solvent: ethyl acetate: hexane = 1: 2), and 4′-isopropyl chalcone (C ₁₈ H ₁₈ O) was purified. Obtained as a yellow oil.
Yield: 1.8 g, Yield: 72%
IR (KBr): 3028 (ν _ArC-H ), 2962 (ν _CH ), 1663 (ν _{C = O} ), 1609 (ν _{C = C} ), 834 (γ _CH ), 768 and 694 cm ^-1 (γ _CH ).
¹ H-NMR (δ, CDCl ₃ , 500 MHz): 1.30 (6H, d, J = 7.0 Hz, CH ₃ ), 2.99 (1H, sept, J = 7.0 Hz, CH), 7.36 (2H, d, J = 8.5 Hz, C _{3 ', 5'} -H), 7.39-7.45 (3H, m, C _3,4,5- H), 7.54 (1H, d, J = 16 Hz, C _α -H), 7.63- 7.67 (2H, m, C _2,6 -H), 7.80 (1H, d, J = 16 Hz, C _β -H), and 7.97 ppm (2H, d, J = 8.5 Hz, C _{2 ', 6'} -H).
Elemental analysis (EA): C ₁₈ H ₁₈ O / 0.5H ₂ O
Theoretical value: C, 83.36%, H, 7.38%
Actual value: C, 83.60%, H, 7.36%

Example 3
3.40 g (10.3 mmol) of 3′-hydroxyacetophenone and 1.0 ml (10.2 mmol) of benzaldehyde were dissolved in 10 ml of 10 wt% aqueous sodium hydroxide solution and 10 ml of ethanol, and stirred at room temperature for 24 hours. To this reaction solution, 200 ml of water and 20 ml of 1M hydrochloric acid were added and extracted with 50 ml of chloroform. After desolvation, 3′-hydroxychalcone (C ₁₅ H ₁₂ O ₂ ) was obtained as a yellow solid.
Yield: 2.1 g, Yield: 91%, Melting point: 117.5-119.0 ° C
IR (KBr): 3203 (ν _OH ), 3058 (ν _ArC-H ), 1654 (ν _{C = O} ), 1610 (ν _{C = C} ), 1447 (δ _OH ), 758 and 683 cm ^-1 (γ _CH ).
¹ H-NMR (δ, CDCl ₃ , 500 MHz): 7.09 (1H, dd, J = 1.5 and 8.6 Hz, C _{4 '} -H), 7.38-7.44 (4H, m, C _3,4,5,5' -H), 7.49-7.53 (2H, m, C _{α, 2 '} -H), 7.59 (1H, d, J = 8.6 Hz, C _6' -H), 7.64-7.66 (2H, m, C _{2, 6} -H), and 7.82 ppm (1H, d, J = 15.5 Hz, C _β -H).

Example 4
(1) Synthesis of 4 '-(1H-tetrazo-5-yl) acetophenone
A suspension of 4'-cyanoacetophenone 1.5 g (10.3 mmol), sodium azide 840 mg (13.0 mmol) and triethylamine hydrochloride 1.8 g (13.0 mmol) in dry toluene (30 ml) was stirred at 95 ° C for 24 hours. After cooling to room temperature, 20 ml of 2M aqueous sodium hydroxide solution was added to terminate the reaction, the aqueous phase was separated, and 80 ml of 6M hydrochloric acid was added to this aqueous phase. The precipitated solid was collected by filtration and purified by drying and recrystallization with methanol to obtain 4 ′-(1H-tetrazo-5-yl) acetophenone (C ₇ H ₈ N ₄ O) as a white solid.
Yield: 1.8 g, Yield: 95%, Melting point: 190.8-191.5 ° C
IR (KBr): 3355 (ν _NH ), 3024 (ν _ArC-H ), 1678 (ν _{C = O} ), 1572 (ν _{N = N} ), 1329 (ν _CN ), and 844 cm ^-1 (γ _CH ) .
¹ H-NMR (δ, CDCl ₃ , 500 MHz): 2.64 (3H, s, CH ₃ ), 8.04 (2H, d, J = 8.6 Hz, C _{3 ', 5'} -H), and 8.19 ppm (2H, d, J = 8.6 Hz, C _{2 ', 6'} -H).

(2) Synthesis of chalcone compounds
4 '-(1H-tetrazo-5-yl) acetophenone 500 mg (2.66 mmol) and benzaldehyde 0.3 ml (3.0 mmol) were dissolved in 10 wt% aqueous sodium hydroxide solution 3 ml and ethanol 3 ml and stirred at room temperature for 24 hours. . To this reaction solution, 30 ml of water and 6 ml of 1M hydrochloric acid were added, and the precipitated solid was collected by filtration, and 4 ′-(1H-tetrazo-5-yl) chalcone (C ₁₆ H ₁₂ N ₄ O) was a pale yellow solid. Got as.
Yield: 732 mg, Yield: 99%, Melting point: 178.1-181.0 ° C
IR (KBr): 3365 (ν _NH ), 3026 (ν _ArC-H ), 1660 (ν _{C = O} ), 1610 (ν _{C = C} ), 1575 (ν _{N = N} ), 1337 (ν _CN ), 840 (δ _CH ), 745 and 691 cm ^-1 (γ _CH ).
¹ H-NMR (δ, DMSO-d ₆ , 500 MHz): 7.48-7.49 (3H, m, C _3,4,5- H), 7.54 (1H, d, J = 15.5 Hz, C _α -H), 7.92-7.94 (2H, m, C _2,6 -H), 8.01 (1H, d, J = 15.5 Hz, C _β -H), 8.24 (2H, d, J = 8.6 Hz, C _{3 ', 5'} -H), and 8.37 ppm (2H, d, J = 8.6 Hz, C _{2 ', 6'} -H).

Example 5
Methyl 5-acetylsalicylate (2.0 g, 10.3 mmol) and benzaldehyde (1.1 ml, 11.1 mmol) were dissolved in 10 wt% aqueous sodium hydroxide solution (10 ml) and ethanol (10 ml), and the mixture was stirred at room temperature for 24 hours. 100 ml of water and 20 ml of 1M hydrochloric acid were added to the reaction solution, and the precipitated solid was collected by filtration to obtain 3′-carboxy-4′-hydroxychalcone (C ₁₆ H ₁₂ O ₄ ) as a pale yellow solid.
Yield: 2.3 g, Yield: 79%, Melting point: 238.2-239.3 ° C
IR (KBr): 3061 (ν _ArC-H ), 1679 (ν _{C = O} ), 1648 (ν _{C = O} ), 1593 (ν _{C = C} ), 1415 (δ _OH ), 1285 (ν _CO ), 865 and 846 (δ _CH ), 761 and 698 cm ^-1 (γ _CH ).
¹ H-NMR (δ, DMSO-d ₆ , 500 MHz): 7.08 (1H, d, J = 9.0 Hz, C _{5 '} -H), 7.41-7.43 (3H, m, C _3,4,5 -H) , 7.54 (1H, d, J = 15.5 Hz, C _α -H), 7.64-7.66 (2H, m, C _2,6 -H), 7.84 (1H, d, J = 15.5 Hz, C _β -H) , 8.19 (1H, dd, J = 2.0 and 9.0 Hz, C _{6 '} -H), and 8.62 ppm (1H, d, J = 2.0 Hz, C _2' -H).

Example 6
4'-Hydroxy-3'-nitroacetophenone (1.82 g, 10.0 mmol) and benzaldehyde (1.0 ml, 10.2 mmol) were dissolved in 10 wt% aqueous sodium hydroxide solution (10 ml) and ethanol (10 ml) and stirred at room temperature for 24 hours. 50 ml of water and 20 ml of 1M hydrochloric acid were added to the reaction solution, and the precipitated solid was collected by filtration to obtain 4′-hydroxy-3′-nitrochalcone (C ₁₅ H ₁₁ NO ₄ ) as a yellow solid.
Yield: 2.3 g, Yield: 86%, Melting point: 156.1-158.0 ° C
IR (KBr): 3224 (ν _OH ), 3085 (ν _ArC-H ), 1658 (ν _{C = O} ), 1592 (ν _{C = C} ), 1533 and 1345 (ν _{N = O} ), 1413 (δ _OH ) , 860 and 822 cm ^-1 (γ _CH ).
¹ H-NMR (δ, CDCl ₃ , 500 MHz): 7.31 (1H, d, J = 9.0 Hz, C _{5 '} -H), 7.45-7.46 (3H, m, C _3,4,5 -H), 7.52 (1H, d, J = 15.5 Hz, C _α -H), 7.67-7.69 (2H, m, C _2,6 -H), 7.89 (1H, d, J = 15.5 Hz, C _β -H), 8.32 (1H, dd, J = 1.7 and 9.0 Hz, C _{6 '} -H), and 8.83 ppm (1H, d, J = 1.7 Hz, C _2' -H).

Example 7
200 mg (0.70 mmol) of 2′-bromochalcone was dissolved in 10 ml of chloroform, 0.1 ml (2.0 mmol) of bromine was further added at 10-20 ° C., and the mixture was stirred for 1 hour at room temperature. 30 ml of chloroform was added to the reaction solution, and the mixture was washed with 40 ml of 10 wt% aqueous sodium thiosulfate solution and 40 ml of saturated brine. Desolvation gave 2,3-dibromo-3-phenyl-1- (2-bromophenyl) -1-propanone (C ₁₅ H ₁₁ OBr ₃ ) as a white solid.
Yield: 282 mg, Yield: 92%, Melting point: 88.2-89.5 ° C
IR (KBr): 3027 (ν _ArC-H ), 1698 (ν _{C = O} ), 776 (γ _CH ), 745 and 695 (γ _CH ), and 580 cm ^-1 (ν _C-Br ).
¹ H-NMR (δ, CDCl ₃ , 500 MHz): 5.59 (1H, d, J = 11.5 Hz, C _β -H), 5.78 (1H, d, J = 11.5 Hz, C _α -H), 7.36-7.50 (7H, m, C _{4 ', 5'} -H and Ph-H), 7.72 (1H, dd, J = 1.2 and 8.0 Hz, C _{6 '} -H), and 7.80 ppm (1H, dd, J = 1.7 and 8.0 Hz, C _{3 '} -H).
Elemental analysis (EA): C ₁₅ H ₁₁ OBr ₃
Theoretical value: C, 40.31%, H, 2.48%
Actual value: C, 40.45%, H, 2.31%

Example 8
200 mg (0.60 mmol) of 2′-iodochalcone was dissolved in 10 ml of chloroform, 0.1 ml (2.0 mmol) of bromine was further added at 10-20 ° C., and the mixture was stirred for 1 hour at room temperature. 30 ml of chloroform was added to the reaction solution, and the mixture was washed with 40 ml of 10 wt% aqueous sodium thiosulfate solution and 40 ml of saturated brine. Desolvation gave 2,3-dibromo-3-phenyl-1- (2-iodophenyl) -1-propanone (C ₁₅ H ₁₁ OBr ₂ I) as a white solid.
Yield: 266 mg, Yield: 90%, Melting point: 132.0-134.2 ° C
IR (KBr): 3005 (ν _ArC-H ), 1696 (ν _{C = O} ), 775 (γ _CH ), 743 and 697 (γ _CH ), and 584 cm ^-1 (ν _C-Br ).
¹ H-NMR (δ, CDCl ₃ , 500MHz): 5.61 (1H, d, J = 11.5 Hz, C _β -H), 5.69 (1H, d, J = 11.5 Hz, C _α -H), 7.23 (1H , td, J = 1.7 and 8.0 Hz, C _{4 '} -H), 7.38-7.52 (6H, m, C _5' -H and Ph-H), 7.83 (1H, dd, J = 1.7 and 8.0 Hz, C _{6 '} -H), and 8.06 ppm (1H, dd, J = 1.0 and 8.0 Hz, C _3' -H).
Elemental analysis (EA): C ₁₅ H ₁₁ OBr ₂ I
Theoretical value: C, 36.47%, H, 2.24%
Actual value: C, 36.59%, H, 2.08%

Example 9
200 mg (0.88 mmol) of 2′-fluorochalcone was dissolved in 10 ml of chloroform, 0.1 ml (2.0 mmol) of bromine was further added at 10-20 ° C., and the mixture was stirred for 1 hour at room temperature. 30 ml of chloroform was added to the reaction solution, and the mixture was washed with 40 ml of 10 wt% aqueous sodium thiosulfate solution and 40 ml of saturated brine. Desolvation gave 2,3-dibromo-3-phenyl-1- (2-fluorophenyl) -1-propanone (C ₁₅ H ₁₁ OBr ₂ F) as a white solid.
Yield: 298 mg, Yield: 88%, Melting point: 95.2-96.3 ° C
IR (KBr): 3030 (ν _ArC-H ), 1686 (ν _{C = O} ), 1214 (ν _CF ), 794 (γ _CH ), 759 and 693 (γ _CH ), and 583 cm ^-1 (ν _{C- Br} ).
¹ H-NMR (δ, CDCl ₃ , 500 MHz): 5.59 (1H, d, J = 11.5 Hz, C _β -H), 5.78 (1H, d, J = 11.5 Hz, C _α -H), 7.21-7.25 (1H, m, C _{5 '} -H), 7.32-7.52 (6H, m, C _4' -H and Ph-H), 7.60-7.66 (1H, m, C _{6 '} -H), and 8.04-8.07 ppm (1H, m, C _{3 '} -H).
Elemental analysis (EA): C ₁₅ H ₁₁ OBr ₂ F
Theoretical value: C, 46.67%, H, 2.87%
Actual value: C, 46.95%, H, 2.88%

Example 10
3′-Iodochalcone 300 mg (0.90 mmol) was dissolved in chloroform 10 ml, bromine 0.1 ml (2.0 mmol) was further added at 10-20 ° C., and the mixture was stirred at room temperature for 1 hour. 30 ml of chloroform was added to the reaction solution, and the mixture was washed with 40 ml of 10 wt% aqueous sodium thiosulfate solution and 40 ml of saturated brine. Desolvation gave 2,3-dibromo-3-phenyl-1- (3-iodophenyl) -1-propanone (C ₁₅ H ₁₁ OBr ₂ I) as a white solid.
Yield: 400 mg, Yield: 90%, Melting point: 132.1-134.5 ° C
IR (KBr): 3060 (ν _ArC-H ), 1686 (ν _{C = O} ), 786 and 671 (γ _CH ), 743 and 693 (γ _CH ), and 581 cm ^-1 (ν _C-Br ).
¹ H-NMR (δ, CDCl ₃ , 500MHz): 5.62 (1H, d, J = 11.5 Hz, C _β -H), 5.73 (1H, d, J = 11.5 Hz, C _α -H), 7.30 (1H , t, J = 8.0 Hz, C _{5 '} -H), 7.39-7.53 (5H, m, Ph-H), 7.99 (1H, d, J = 8.0 Hz, C _4' -H), 8.05 (1H, d, J = 8.0 Hz, C _{6 '} -H), and 8.40 ppm (1H, s, C _2' -H).
Elemental analysis (EA): C ₁₅ H ₁₁ OBr ₂ I
Theoretical value: C, 36.47%, H, 2.24%
Actual value: C, 36.55%, H, 2.22%

Example 11
4'-Iodochalcone 200 mg (0.60 mmol) was dissolved in chloroform 10 ml, bromine 0.1 ml (2.0 mmol) was further added at 10-20 ° C, and the mixture was stirred for 1 hour at room temperature. 30 ml of chloroform was added to the reaction solution, and the mixture was washed with 40 ml of 10 wt% aqueous sodium thiosulfate solution and 40 ml of saturated brine. Desolvation gave 2,3-dibromo-3-phenyl-1- (4-iodophenyl) -1-propanone (C ₁₅ H ₁₁ OBr ₂ I) as a white solid.
Yield: 238 mg, Yield: 82%, Melting point: 160.8-163.5 ° C
IR (KBr): 3024 (ν _ArC-H ), 1685 (ν _{C = O} ), 837 (γ _CH ), 749 and 694 (γ _CH ), and 579 cm ^-1 (ν _C-Br ).
¹ H-NMR (δ, CDCl ₃ , 500 MHz): 5.61 (1H, d, J = 11.5 Hz, C _β -H), 5.74 (1H, d, J = 11.5 Hz, C _α -H), 7.38-7.53 (5H, m, Ph-H), 7.80 (2H, d, J = 8.5 Hz, C _{3 ', 5'} -H), and 7.09 ppm (2H, d, J = 8.5 Hz, C _{2 ', 6'} -H).
Elemental analysis (EA): C ₁₅ H ₁₁ OBr ₂ I
Theoretical value: C, 36.47%, H, 2.24%
Actual value: C, 36.76%, H, 1.95%

Example 12
300 mg (1.19 mmol) of 2′-carboxychalcone was dissolved in 20 ml of chloroform, 0.1 ml (2.0 mmol) of bromine was further added at 10-20 ° C., and the mixture was stirred for 1 hour at room temperature. The reaction solution was washed with 40 ml of 10 wt% aqueous sodium thiosulfate solution and 40 ml of saturated brine. Removal of the solvent gave 2,3-dibromo-3-phenyl-1- (2-carboxyphenyl) -1-propanone (C ₁₆ H ₁₂ O ₃ Br ₂ ) as a white solid.
Yield: 382 mg, Yield: 78%, Melting point: 164.0-165.1 ° C
IR (KBr): 3036 (ν _ArC-H ), 2677 (ν _OH) , 1683 (ν _{C = O} ), 1413 (δ _OH ), 1219 (ν _{C = O} ), 742 and 696 (γ _CH ), and 566 cm ^-1 (ν _C-Br ).
¹ H-NMR (δ, CDCl ₃ , 500 MHz): 5.58 (1H, d, J = 11.5 Hz, C _β -H), 5.70 (1H, d, J = 11.5 Hz, C _α -H), 7.30-7.48 (5H, m, Ph-H), 7.66-7.68 (1H, m, C _{4 '} -H), 7.79 (1H, d, J = 1.5 and 8.6 Hz, C _6' -H), 7.85-7.90 (1H , m, C _{5 '} -H), and 7.96 ppm (1H, d, J = 1.5 and 8.6 Hz, C _3' -H).

Example 13
300 mg (1.19 mmol) of 3′-carboxychalcone was dissolved in 35 ml of chloroform, and 0.1 ml (2.0 mmol) of bromine was further added at 10-20 ° C., followed by stirring at room temperature for 1 hour. The reaction solution was washed with 40 ml of 10 wt% aqueous sodium thiosulfate solution and 40 ml of saturated brine. Desolvation gave 2,3-dibromo-3-phenyl-1- (3-carboxyphenyl) -1-propanone (C ₁₆ H ₁₂ O ₃ Br ₂ ) as a white solid.
Yield: 311 mg, Yield: 64%, Melting point: 179.0-180.3 ° C
IR (KBr): 3001 (ν _ArC-H ), 2856 (ν _OH ), 1690 (ν _{C = O} ), 1413 (δ _OH ), 1263 (ν _CO ), 758 and 697 (γ _CH ), and 566 cm ^-1 (ν _C-Br ).
¹ H-NMR (δ, CDCl ₃ , 500 MHz): 5.66 (1H, d, J = 11.5 Hz, C _β -H), 5.86 (1H, d, J = 11.5 Hz, C _α -H), 7.38-7.56 (5H, m, Ph-H), 7.70 (1H, t, J = 8.6 Hz, C _{5 '} -H), 8.35-8.39 (2H, m, C _{4', 6 '} -H), and 8.77 ppm ( 1H, s, C _{2 '} -H).
Elemental analysis (EA): C ₁₆ H ₁₂ O ₃ Br ₂・ 0.2H ₂ O
Theoretical value: C, 46.23%, H, 3.01%
Actual value: C, 45.98%, H, 3.23%

Example 14
4'-Carboxychalcone 200 mg (0.79 mmol) was dissolved in chloroform 80 ml, bromine 0.1 ml (2.0 mmol) was further added at 10-20 ° C, and the mixture was stirred at room temperature for 1 hour. The reaction solution was washed with 40 ml of 10 wt% aqueous sodium thiosulfate solution and 40 ml of saturated brine. Desolvation gave 2,3-dibromo-3-phenyl-1- (4-carboxyphenyl) -1-propanone (C ₁₆ H ₁₂ O ₃ Br ₂ ) as a white solid.
Yield: 116 mg, Yield: 36%, Melting point: 213.0-215.0 ° C
IR (KBr): 2986 (ν _ArC-H ), 2877 (ν _OH ), 1691 (ν _{C = O} ), 1405 (δ _OH ), 1288 (ν _CO ), 796 (γ _CH) , 732 and 696 (γ _CH ), and 582 cm ^-1 (ν _C-Br ).
¹ H-NMR (δ, CDCl ₃ , 500 MHz): 5.64 (1H, d, J = 11.5 Hz, C _β -H), 5.81 (1H, d, J = 11.5 Hz, C _α -H), 7.41-7.54 (5H, m, Ph-H), 8.19 (2H, d, J = 8.0 Hz, C _{2 ', 6'} -H), and 8.27 ppm (2H, d, J = 8.0 Hz, C _{3 ', 5'} -H).
Elemental analysis (EA): C ₁₆ H ₁₂ O ₃ Br ₂・ 0.2H ₂ O
Theoretical value: C, 46.23%, H, 3.01%
Actual value: C, 46.10%, H, 2.96%

Example 15
300 mg (1.33 mmol) of 3′-hydroxychalcone was dissolved in 50 ml of chloroform, 0.1 ml (2.0 mmol) of bromine was further added at 10-20 ° C., and the mixture was stirred for 1 hour at room temperature. The reaction solution was washed with 40 ml of 10 wt% aqueous sodium thiosulfate solution and 40 ml of saturated brine. Desolvation gave 2,3-dibromo-3-phenyl-1- (3-hydroxyphenyl) -1-propanone (C ₁₅ H ₁₂ O ₂ Br ₂ ) as a white solid.
Yield: 389 mg, Yield: 76%, Melting point: 139.8-141.3 ° C
IR (KBr): 3463 (ν _OH ), 3030 (ν _ArC-H ), 1677 (ν _{C = O} ), 1447 (δ _OH ), 1334 (ν _CO ), 808 and 676 (γ _CH ), and 572 cm ^-1 (ν _C-Br ).
¹ H-NMR (δ, CDCl ₃ , 500MHz): 5.62 (1H, d, J = 11.5 Hz, C _β -H), 5.77 (1H, d, J = 11.5 Hz, C _α -H), 7.15 (1H , dd, J = 1.7 and 8.6 Hz, C _{4 '} -H), 7.38-7.55 (7H, m, C _{2', 5 '} -H and Ph-H), and 7.66 ppm (1H, d, J = 8.6 Hz, C _{3 '} -H).

Example 16
4'-Isopropylchalcone 300 mg (1.20 mmol) was dissolved in chloroform 10 ml, bromine 0.1 ml (2.0 mmol) was further added at 10-20 ° C, and the mixture was stirred at room temperature for 1 hour. To the reaction solution, 30 ml of chloroform was added and washed with 40 ml of 10 wt% aqueous sodium thiosulfate solution and 40 ml of saturated brine. After removing the solvent, the obtained crude product was purified by silica gel column chromatography (silica gel: 30 g, developing solvent: ethyl acetate: hexane = 1: 2), and 2,3-dibromo-3-phenyl-1- ( 4-isopropylphenyl) -1-propanone _{(C 18 H 18 OBr 2)} , as a brown solid.
Yield: 360 mg, Yield: 74%, Melting point: 113.1-115.9 ° C
IR (KBr): 2962 (ν _ArC-H ), 1686 (ν _{C = O} ), 848 (γ _CH ), 764 and 693 (γ _CH ), and 582 cm ^-1 (ν _C-Br ).
¹ H-NMR (δ, CDCl ₃ , 500 MHz): 1.30 (6H, d, J = 7.0 Hz, CH ₃ ), 3.01 (1H, sept, J = 7.0 Hz, CH), 5.64 (1H, d, J = 11.5 Hz, C _β -H), 5.82 (1H, d, J = 11.5Hz, C _α -H), 7.38-7.47 (5H, m, Ph-H), 7.53 (2H, d, J = 8.5 Hz, C _{3 ', 5'} -H), and 8.04 ppm (2H, d, J = 8.5 Hz, C _{2 ', 6'} -H).
Elemental analysis (EA): C ₁₈ H ₁₈ OBr ₂
Theoretical value: C, 52.71%, H, 4.42%
Actual value: C, 52.94%, H, 4.66%

Example 17
350 mg (1.30 mmol) of 4′-hydroxy-3′-nitrochalcone was dissolved in 10 ml of chloroform, 0.1 ml (2.0 mmol) of bromine was further added at 10-20 ° C., and the mixture was stirred for 1 hour at room temperature. To the reaction solution, 30 ml of chloroform was added and washed with 40 ml of 10 wt% aqueous sodium thiosulfate solution and 40 ml of saturated brine. Removal of the solvent gave 2,3-dibromo-3-phenyl-1- (4-hydroxy-3-nitrophenyl) -1-propanone (C ₁₅ H ₁₁ NO ₄ Br ₂ ) as a pale yellow solid.
Yield: 453 mg, Yield: 82%, Melting point: 167.2-169.5 ° C
IR (KBr): 3144 (ν _OH ), 3073 (ν _ArC-H ), 1680 (ν _{C = O} ), 1550 and 1325 (ν _{N = O} ), 1413 (δ _OH ), 906 and 824 (γ _CH ) , and 586 cm ^-1 (ν _C-Br ).
¹ H-NMR (δ, CDCl ₃ , 500MHz): 5.63 (1H, d, J = 11.5 Hz, C _β -H), 5.78 (1H, d, J = 11.5 Hz, C _α -H), 7.34 (1H , d, J = 8.5 Hz, C _{5 '} -H), 7.40-7.55 (5H, m, Ph-H), 8.35 (1H, dd, J = 1.6 and 8.5 Hz, C _6' -H), and 8.87 ppm (1H, d, J = 1.6 Hz, C _{2 '} -H).

Example 18
4'-Hydroxychalcone 300 mg (1.34 mmol) was dissolved in chloroform 50 ml, bromine 0.1 ml (2.0 mmol) was further added at 10-20 ° C., and the mixture was stirred at room temperature for 1 hour. The reaction solution was washed with 40 ml of 10 wt% aqueous sodium thiosulfate solution and 40 ml of saturated brine. After removing the solvent, the obtained crude product was purified by silica gel column chromatography (silica gel: 30 g, developing solvent: ethyl acetate: hexane = 1: 2), and 2,3-dibromo-3-phenyl-1- ( 3-bromo-4-hydroxyphenyl) -1-propanone _{(C 15 H 11 O 2 Br} 3), as a white solid.
Yield: 312 mg, Yield: 55%, Melting point: 155.6-158.1 ° C
IR (KBr): 3339 (ν _OH ), 3061 (ν _ArC-H ), 1664 (ν _{C = O} ), 828 (γ _CH ), 757 and 692 (γ _CH ), and 588 cm ^-1 (ν _{C- Br} ).
¹ H-NMR (δ, CDCl ₃ , 500MHz): 5.62 (1H, d, J = 11.5 Hz, C _β -H), 5.72 (1H, d, J = 11.5 Hz, C _α -H), 7.16 (1H , d, J = 8.6 Hz, C _{5 '} -H), 7.37-7.53 (5H, m, Ph), 8.00 (1H, dd, J = 2.3 and 8.5 Hz, C _6' -H), and 8.27 ppm ( 1H, d, J = 8.5 Hz, C _{2 '} -H).
Elemental analysis (EA): C ₁₅ H ₁₁ O ₂ Br ₃
Theoretical value: C, 38.92%, H, 2.39%
Actual value: C, 38.91%, H, 2.56%

Example 19
A suspension of 4′-hydroxychalcone 300 mg (1.33 mmol) and 5% palladium carbon 40 mg in ethanol 20 ml was stirred at room temperature for 24 hours under a hydrogen atmosphere. After removing the catalyst by filtration and removing the solvent, 3-phenyl-1- (4-hydroxyphenyl) -1-propanone (C ₁₅ H ₁₄ O ₂ ) was obtained as a colorless oil.
Yield: 273 mg, Yield: 87%
IR (KBr): 3451 (ν OH), 3022 (ν ArC-H), 1690 (ν C = O), 1413 (δ OH), 1287 (ν CO), 808 (δ CH), 777 and 695 cm - ¹ (γ _CH ).
¹ H-NMR (δ, CDCl ₃ , 500 MHz): 2.58 (1H, t, J = 7.0 Hz, C _β -H), 2.63 (1H, t, J = 7.0 Hz, C _α -H), 6.75 (2H , d, J = 8.5 Hz, C _{3 ', 5'} -H), 7.05 (2H, d, J = 8.6 Hz, C _{2 ', 6'} -H), and 7.14-7.29 ppm (5H, m, Ph -H).

Example 20
(1) Introduction of hydroxyl protecting group (Boc group) 4'-hydroxychalcone 1.0 g (4.46 mmol), di-tert-butyl dicarbonate 0.95 g (4.92 mmol) and triethylamine 0.7 ml (5.02 mmol) were dried in THF40. It was dissolved in ml and stirred at room temperature for 24 hours. After removing the solvent, the residue was dissolved in 40 ml of ethyl acetate and washed with 40 ml of 5 wt% aqueous sodium hydrogen carbonate solution, 40 ml of 1M hydrochloric acid and 40 ml of saturated brine. Drying and solvent removal gave 4 ′-(tert-butoxycarbonyloxy) chalcone (C ₂₀ H ₂₀ O ₄ ) as a pale yellow solid.
Yield: 1.5 g, Yield: 100%, Melting point: 116.5-118.0 ° C
IR (KBr): 2999 (ν _ArC-H ), 1753 (ν _{C = O} ), 1658 (ν _{C = O} ), 1599 (ν _{C = C} ), 751 and 691 cm ^-1 (γ _CH ).
¹ H-NMR (δ, CDCl ₃ , 500MHz): 1.58 (9H, s, Boc), 7.32 (2H, d, J = 8.6 Hz, C _{3 ', 5'} -H), 7.41-7.44 (3H, m , C _3,4,5- H), 7.50 (1H, d, J = 15.5 Hz, C _α -H), 7.64-7.66 (2H, m, C _2,6 -H), 7.82 (1H, d, J = 15.5 Hz, C _β -H), and 8.06 ppm (2H, d, J = 8.6 Hz, C _{2 ', 6'} -H).

(2) Bromination reaction 300 mg (0.92 mmol) of 4 ′-(tert-butoxycarbonyloxy) chalcone obtained above was dissolved in 10 ml of chloroform, and 0.1 ml (2.0 mmol) of bromine at 10-20 ° C. ) Was added and stirred at room temperature for 1 hour. Chloroform 30 ml was added to this reaction liquid, and it was washed with 10 wt% sodium thiosulfate aqueous solution 40 ml and saturated saline 40 ml. After removing the solvent, the obtained crude product was purified by silica gel column chromatography (silica gel: 30 g, developing solvent: ethyl acetate: hexane = 1: 2), and 2,3-dibromo-3-phenyl-1- ( 4-tert-butoxycarbonyl oxyphenyl) -1-propanone _{(C 20 H 20 O 4 Br} 2), as a white solid.
Yield: 316 mg, Yield: 71%, Melting point: 142.5-144.8 ° C
IR (KBr): 2980 (ν _ArC-H ), 1762 (ν _{C = O} ), 1685 (ν _{C = O} ), 855 (γ _CH ), 766 and 693 (γ _CH ), and 579 cm ^-1 (ν _C-Br ).
¹ H-NMR (δ, CDCl ₃ , 500 MHz): 1.58 (9H, s, Boc), 5.63 (1H, d, J = 11.5 Hz, C _β -H), 5.78 (1H, d, J = 11.5 Hz, C _α -H), 7.36-7.45 (5H, m, C _{3,4,5,3 ', 5'} -H), 7.51-7.53 (2H, m, C _2,6 -H), and 8.14 ppm ( 2H, d, J = 8.6 Hz, C _{2 ', 6'} -H).

(3) Deprotection reaction 2,3-dibromo-3-phenyl-1- (4-tert-butoxycarbonyloxyphenyl) -1-propanone (250 mg, 0.52 mmol) obtained above was added to 10 ml of dry dichloromethane. After dissolution, 0.2 ml (2.6 mmol) of trifluoroacetic acid was added at 0 ° C., and the mixture was stirred at room temperature for 24 hours under an argon atmosphere. The reaction was terminated by adding 10 ml of 5 wt% aqueous sodium hydrogen carbonate solution, and the organic phase was separated and dried. After removing the solvent, the obtained crude product was purified by silica gel column chromatography (silica gel: 30 g, developing solvent: ethyl acetate), and 2,3-dibromo-3-phenyl-1- (4-hydroxyphenyl)- 1-propanone (C ₁₅ H ₁₂ O ₂ Br ₂ ) was obtained as a pale yellow solid.
Yield: 162 mg, Yield: 81%, Melting point: 155.5-156.5 ° C
IR (KBr): 3296 (ν _OH ), 3025 (ν _ArC-H ), 1656 (ν _{C = O} ), 1421 (δ _OH ), 847 (γ _CH ), 756 and 689 (γ _CH ), and 577 cm ^-1 (ν _C-Br ).
¹ H-NMR (δ, CDCl ₃ , 500MHz): 5.64 (1H, d, J = 11.5 Hz, C _β -H), 5.78 (1H, d, J = 11.5 Hz, C _α -H), 6.96 (2H , d, J = 8.6 Hz, C _{3 ', 5'} -H), 7.37-7.54 (5H, m, Ph-H), and 8.05 ppm (2H, d, J = 8.6 Hz, C _{2 ', 6'} -H).
Elemental analysis (EA): C ₁₅ H ₁₂ O ₂ Br ₂
Theoretical value: C, 46.91%, H, 3.15%
Actual value: C, 46.81%, H, 3.15%

Example 21
(1) Introduction of hydroxyl-protecting group (Boc group) 4'-hydroxy-3'-methylchalcone 1.0 g (4.20 mmol), di-tert-butyl dicarbonate 0.95 g (4.92 mmol) and triethylamine 0.7 ml (5.02 mmol) ) Was dissolved in 40 ml of dry THF and stirred at room temperature for 24 hours. After removing the solvent, the residue was dissolved in 40 ml of ethyl acetate and washed with 40 ml of 5 wt% aqueous sodium hydrogen carbonate solution, 40 ml of 1M hydrochloric acid and 40 ml of saturated brine. Drying and solvent removal gave 4 ′-(tert-butoxycarbonyloxy) -3′-methylchalcone (C ₂₁ H ₂₂ O ₄ ) as a yellow solid.
Yield: 1.4 g, Yield: 100%, Melting point: 104.5-106.2 ° C
IR (KBr): 2986 (ν ArC-H), 1750 (ν C = O), 1665 (ν C = O), 1610 (ν C = C), 888 and 830 (γ CH), 751 and 691 cm - ¹ (γ _CH ).
¹ H-NMR (δ, CDCl ₃ , 500MHz): 1.58 (9H, s, Boc), 2.40 (3H, s, CH ₃ ), 7.24 (1H, d, J = 8.6 Hz, C _{5 '} -H), 7.41-7.44 (3H, m, C _3,4,5- H), 7.50 (1H, d, J = 15.5 Hz, C _α -H), 7.63-7.66 (2H, m, C _2,6 -H) , 7.80 (1H, d, J = 15.5 Hz, C _β -H), 7.88 (1H, dd, J = 1.7 and 8.6 Hz, C _{6 '} -H), and 7.91 ppm (1H, d, J = 1.7 Hz , C _{2 '} -H).

(2) Bromination reaction 600 mg (1.8 mmol) of 4 ′-(tert-butoxycarbonyloxy) -3′-methylchalcone obtained above was dissolved in 20 ml of chloroform, and bromine was further removed at 10-20 ° C. 0.2 ml (4.0 mmol) was added and it stirred at room temperature for 1 hour. To this reaction solution, 30 ml of chloroform was added and washed with 50 ml of 10 wt% aqueous sodium thiosulfate solution and 50 ml of saturated brine. After removing the solvent, the obtained crude product was purified by silica gel column chromatography (silica gel: 30 g, developing solvent: ethyl acetate: hexane = 1: 2), and 2,3-dibromo-3-phenyl-1- ( 4-tert-Butoxycarbonyloxy-3-methylphenyl) -1-propanone (C ₂₁ H ₂₂ O ₄ Br ₂ ) was obtained as a white solid.
Yield: 465 mg, Yield: 53%, Melting point: 165.2-167.1 ° C
IR (KBr): 2986 (ν _ArC-H ), 1750 (ν _{C = O} ), 1688 (ν _{C = O} ), 890 and 836 (γ _CH ), 756 and 693 (γ _CH ), and 587 cm ^-1 (ν _C-Br ).
¹ H-NMR (δ, CDCl ₃ , 500 MHz): 1.58 (9H, s, Boc), 2.40 (3H, s, CH ₃ ), 5.63 (1H, d, J = 11.5 Hz, C _β -H), 5.78 (1H, d, J = 11.5 Hz, C _α -H), 7.29 (1H, d, J = 8.0 Hz, C _{5 '} -H), 7.36-7.54 (5H, m, Ph-H), 7.96 (1H , dd, J = 1.7 and 8.0 Hz, C _{6 '} -H), and 7.99 ppm (1H, d, J = 1.7 Hz, C _2' -H).

(3) Deprotection reaction 500 mg (1.0 mmol) of 2,3-dibromo-3-phenyl-1- (4-tert-butoxycarbonyloxy-3-methylphenyl) -1-propanone obtained above was dried. It was dissolved in 30 ml of dichloromethane, 0.4 ml (5.2 mmol) of trifluoroacetic acid was added at 0 ° C., and the mixture was stirred at room temperature for 24 hours under an argon atmosphere. To this reaction solution, 30 ml of 5 wt% aqueous sodium hydrogen carbonate solution was added to terminate the reaction, and the organic phase was separated and dried. After removing the solvent, the obtained crude product was purified by silica gel column chromatography (silica gel: 30 g, developing solvent: ethyl acetate), and 2,3-dibromo-3-phenyl-1- (4-hydroxyphenyl)- 1-propanone (C ₁₆ H ₁₄ O ₂ Br ₂ ) was obtained as a pale yellow solid.
Yield: 341 mg, Yield: 85%, Melting point: 178.5-179.8 ° C
IR (KBr): 3336 (ν _OH ), 3058 (ν _ArC-H ), 1655 (ν _{C = O} ), 1421 (δ _OH ), 914 and 830 (γ _CH ), 764 and 698 (γ _CH ), and 589 cm ^-1 (ν _C-Br ).
¹ H-NMR (δ, CDCl ₃ , 500MHz): 2.35 (3H, s, CH ₃ ), 5.65 (1H, d, J = 11.5 Hz, C _β -H), 5.79 (1H, d, J = 11.5 Hz , C _α -H), 6.88 (1H, d, J = 8.0 Hz, C _{5 '} -H), 7.38-7.54 (5H, m, Ph-H), 7.89 (1H, dd, J = 1.6 and 8.0 Hz , C _{6 '} -H), and 7.93 ppm (1H, d, J = 1.6 Hz, C _2' -H).

  The structures of the compounds obtained in Examples 1 to 21 and the compounds used as comparative examples (Chalcone: Tokyo Chemical Industry; product code C0071) are shown in Table 1.

Test Example 1 (Measurement of MIC for bacteria)
A solution obtained by mixing 20 parts by weight of methyl carbitol (diethylene glycol monomethyl ether) and 79 parts by weight of water with respect to 1 part by weight of each of the compounds obtained in Examples 1 to 21 and the compounds mentioned in Comparative Examples Got. Using a microplanter (manufactured by Sakuma Seisakusho), a bacterial suspension for inoculation was inoculated into a glucose broth agar medium (pH 6.0) to which each of these solutions was added, and cultured at 33 ° C. for 18 hours. Subsequently, the growth of the bacterium after the culture was observed to determine the minimum inhibitory concentration MIC (μg / mL).

Test Example 2 (Measurement of MIC for mold and yeast)
Using a microplanter (manufactured by Sakuma Seisakusho), a fungus spore suspension and a yeast for inoculation were inoculated into a glucose broth agar medium (pH 6.0) to which a solution prepared in the same manner as in Test Example 1 was added. The cells were cultured at 18 ° C. for 18 hours, and further cultured at 28 ° C. for 2 days. Subsequently, the growth of the bacterium after the culture was observed to determine the minimum inhibitory concentration MIC (μg / mL).

  Table 2 shows the names of bacteria, molds and yeasts used in the MIC measurement, and the results of Test Examples 1 and 2. In addition, the numerical value in a table | surface shows minimum growth inhibitory concentration MIC (microgram / mL).

  The industrial sterilizing composition containing the chalcone compound or salt thereof of the present invention is excellent in sterilizing, antibacterial, antifungal, antiseptic and antialgal effects, and therefore various industrial waters such as a paper pulp mill and a cooling water circulation process; Water-containing pulp, coated paper, paper coating solution, paint, binder, adhesive, latex, ink, etchant, soaking water, wood, fiber, cement admixture, sealing agent, resin emulsion, building materials Widely applicable to industrial products or industrial raw materials.

Claims (5)

A chalcone compound represented by the following general formula (1) or a salt thereof.

(In the formula, R ¹ represents a hydrogen atom, a halogen atom or a carboxyl group; R ² represents a hydrogen atom, a halogen atom, a carboxyl group, a hydroxyl group, an alkoxy group, a C _1-4 alkyl group or a nitro group; R ³ represents a hydrogen atom, a halogen atom, a carboxyl group, a hydroxyl group, an alkoxy group, a C _1-4 alkyl group or a nitrogen-containing heterocyclic ring, and A represents —CH═CH— or —CHX ¹ —CHX ² —. X ¹ and X ² are the same or different and each represents a hydrogen atom or a halogen atom, provided that when A represents —CH═CH— and R ³ represents a carboxyl group or a hydroxyl group, R ¹ represents hydrogen. Not an atom.) In the general formula (1), the chalcone compound is
(I) a compound wherein A represents —CH═CH—, R ¹ and R ² are as defined above, and R ³ represents a C _1-4 alkyl group,
(Ii) A compound in which A represents —CHX ¹ —CHX ² —, R ¹ or R ² represents a halogen atom, and R ³ is as defined above,
(Iii) A represents —CHX ¹ —CHX ² —, R ¹ is as defined above, R ² or R ³ represents a carboxyl group, and (iv) A represents —CHX ¹ —CHX ² —. A compound in which R ¹ is the same as defined above, and R ² or R ³ represents a hydroxyl group,
The chalcone compound or a salt thereof according to claim 1, which is one selected from the group consisting of: A method for producing a chalcone compound represented by the following general formula (1a) or a salt thereof,

(In the formula, R ¹ represents a hydrogen atom, a halogen atom or a carboxyl group; R ² represents a hydrogen atom, a halogen atom, a carboxyl group, a hydroxyl group, an alkoxy group, a C _1-4 alkyl group or a nitro group; R ³ represents a hydrogen atom, a halogen atom, a carboxyl group, a hydroxyl group, an alkoxy group, a C _1-4 alkyl group or a nitrogen-containing heterocyclic ring, provided that when R ³ represents a carboxyl group or a hydroxyl group, R ¹ is , Not a hydrogen atom.)
An acetophenone compound represented by the following general formula (2);

(In the formula, R ¹ represents a hydrogen atom, a halogen atom or a carboxyl group; R ² represents a hydrogen atom, a halogen atom, a carboxyl group, a hydroxyl group, an alkoxy group, a C _1-4 alkyl group or a nitro group; R ³ represents a hydrogen atom, a halogen atom, a carboxyl group, a hydroxyl group, an alkoxy group, a C _1-4 alkyl group or a nitrogen-containing heterocyclic ring, provided that when R ³ represents a carboxyl group or a hydroxyl group, R ¹ is , Not a hydrogen atom.)
A benzophenone compound represented by the following general formula (3) is reacted in a solvent in the presence of a base;

A method for producing a chalcone compound or a salt thereof. A method for producing a chalcone compound represented by the following general formula (1b) or a salt thereof,

(In the formula, R ¹ represents a hydrogen atom, a halogen atom or a carboxyl group; R ² represents a hydrogen atom, a halogen atom, a carboxyl group, a hydroxyl group, an alkoxy group, a C _1-4 alkyl group or a nitro group; R ³ represents a hydrogen atom, a halogen atom, a carboxyl group, a hydroxyl group, an alkoxy group, a C _1-4 alkyl group or a nitrogen-containing heterocyclic ring, and X ¹ and X ² are the same or different and each represents a hydrogen atom or a halogen atom. Show.)
An addition treatment is performed on the chalcone compound represented by the following general formula (1a).

(In the formula, R ¹ represents a hydrogen atom, a halogen atom or a carboxyl group; R ² represents a hydrogen atom, a halogen atom, a carboxyl group, a hydroxyl group, an alkoxy group, a C _1-4 alkyl group or a nitro group; R ³ represents a hydrogen atom, a halogen atom, a carboxyl group, a hydroxyl group, an alkoxy group, a C _1-4 alkyl group or a nitrogen-containing heterocyclic ring, provided that when R ³ represents a carboxyl group or a hydroxyl group, R ¹ is , Not a hydrogen atom.)
A method for producing a chalcone compound or a salt thereof. An industrial bactericidal composition comprising the chalcone compound or a salt thereof according to claim 1 or 2.